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出境医 / 临床实验 / Study to Compare GI Tolerability Following Oral Administration of Bafiertam™ or Tecfidera to Healthy Volunteers

Study to Compare GI Tolerability Following Oral Administration of Bafiertam™ or Tecfidera to Healthy Volunteers

Study Description
Brief Summary:

The primary objective of the study is to compare in healthy subjects, the GI tolerability of bioequivalent doses of Bafiertam™(monomethyl fumarate) and its pro-drug Tecfidera® (dimethyl fumarate).

Secondary objective of this study is to compare the safety and tolerability of Bafiertam™ and Tecfidera® when administered orally following bioequivalent dose regimens in healthy subjects.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Bafiertam Drug: Tecfidera Phase 1

Detailed Description:
Subjects randomized (1:1) to either Bafiertam (monomethyl fumarate) or Tecfidera (dimethyl fumarate) will enter a double-blind titration period where they will receive either Bafiertam 95 mg twice daily (BID) or Tecfidera 120 mg BID for 7 days. Following the titration period, they will enter a maintenance period in which they will receive Bafiertam 190 mg BID or Tecfidera 240 mg BID for 4 weeks.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Study to Compare Gastrointestinal Tolerability Following Oral Administration of Bafiertam™ (Monomethyl Fumarate) or Tecfidera® (Dimethyl Fumarate) to Healthy Male and Female Volunteers
Actual Study Start Date : July 7, 2019
Actual Primary Completion Date : October 19, 2019
Actual Study Completion Date : October 19, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: Bafiertam
oral capsules administered twice daily
Drug: Bafiertam
Over-encapsulated capsule to mask treatment
Other Name: monomethyl fumarate

Active Comparator: Tecfidera
oral capsules administered twice daily
Drug: Tecfidera
Over-encapsulated capsule to mask treatment
Other Name: dimethyl fumarate

Outcome Measures
Primary Outcome Measures :
  1. Area Under the Curve (AUC) in each of the individual symptoms over the treatment period. [ Time Frame: 5 weeks ]
    The symptoms measured are (1) nausea, (2) vomiting, (3) diarrhea, (4) upper abdominal pain, (5) lower abdominal pain, (6) constipation, (7) bloating, and (8) flatulence


Secondary Outcome Measures :
  1. Comparison of the Modified Overall Gastrointestinal Symptom Scale (MOGISS) composite score [ Time Frame: 5 weeks ]
    The MOGISS assesses global GI events (defined as one or more of the following symptoms: nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, constipation, bloating, and flatulence) and their effect on the patient during the 24 hours before each morning dose. The events items are rated on a 10-point numerical rating scale, where 0 = no events, 1 to 3 = mild events, 4 to 6 = moderate events, 7 to 9 = severe events, and 10 = extreme events. The MOGISS Total (sum of 8 scores) range is 0 (no symptoms) to 80 (worst possible symptoms) and the MOGISS Composite (average of 8 scores) range is 0 (no symptoms) - 10 (worst possible symptoms).

  2. The number of days that a subject experiences at least one GI symptom. [ Time Frame: 5 weeks ]
    Number of days with at (as reported on the MOGISS) with a severity score of at least 1

  3. AUC in the MOGISS total score within in each subject over the treatment period [ Time Frame: 5 weeks ]
    Defined as the daily total of all 8 individual symptom scores within each subject

  4. Frequency, severity, and duration of overall GI events using the MOGISS. [ Time Frame: 5 weeks ]
    Frequency, severity and duration of overall GI events will be completed using the MOGISS for each week of study treatment as well as for the overall study treatment period.

  5. Safety and tolerability outcomes: incidence rates of all non GI-adverse events [ Time Frame: 5 weeks ]
    Subject incidence rates of all non GI-adverse events


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Males or non-pregnant females.
  2. Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator.
  3. Body Mass Index within 18.0 - 34.0 kg/m2, inclusive

Exclusion Criteria:

  1. Known history or presence of any clinically significant hepatic, renal/genitourinary, Gastrointestinal (GI), cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator.
  2. Clinically significant history or presence of any clinically significant GI pathology unresolved GI symptoms, or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within 7 days prior to first study drug administration, as determined by the PI/Sub-Investigator.
  3. Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
  4. Subject with abnormal baseline laboratory values deemed to be clinically significant by the Investigator.
  5. Lymphocyte count <1.5x 10^9/L.
  6. Known history or presence of: Alcohol abuse or dependence within one year prior to first study drug administration; Drug abuse or dependence; Hypersensitivity or idiosyncratic reaction to DMF, its excipients, and/or related substances; Progressive multifocal leukoencephalopathy (PML); Fanconi syndrome; Flushing (e.g., warmth, redness, itching, and burning sensation); Low white blood cell count (lymphopenia);
Contacts and Locations

Locations
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United States, Missouri
BioPharma Services, Inc.
Columbia, Missouri, United States, 65201
Sponsors and Collaborators
Banner Life Sciences LLC
Investigators
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Principal Investigator: Kathleen Doisy, MD BioPharma Services, Inc
Tracking Information
First Submitted Date  ICMJE July 15, 2019
First Posted Date  ICMJE July 17, 2019
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE July 7, 2019
Actual Primary Completion Date October 19, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
Area Under the Curve (AUC) in each of the individual symptoms over the treatment period. [ Time Frame: 5 weeks ]
The symptoms measured are (1) nausea, (2) vomiting, (3) diarrhea, (4) upper abdominal pain, (5) lower abdominal pain, (6) constipation, (7) bloating, and (8) flatulence
Original Primary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
Comparison of the Modified Overall Gastrointestinal Symptom Scale (MOGISS) composite score [ Time Frame: 5 weeks ]
The daily mean of all 8 individual GI symptom scores over the treatment period
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • Comparison of the Modified Overall Gastrointestinal Symptom Scale (MOGISS) composite score [ Time Frame: 5 weeks ]
    The MOGISS assesses global GI events (defined as one or more of the following symptoms: nausea, diarrhea, upper abdominal pain, lower abdominal pain, vomiting, constipation, bloating, and flatulence) and their effect on the patient during the 24 hours before each morning dose. The events items are rated on a 10-point numerical rating scale, where 0 = no events, 1 to 3 = mild events, 4 to 6 = moderate events, 7 to 9 = severe events, and 10 = extreme events. The MOGISS Total (sum of 8 scores) range is 0 (no symptoms) to 80 (worst possible symptoms) and the MOGISS Composite (average of 8 scores) range is 0 (no symptoms) - 10 (worst possible symptoms).
  • The number of days that a subject experiences at least one GI symptom. [ Time Frame: 5 weeks ]
    Number of days with at (as reported on the MOGISS) with a severity score of at least 1
  • AUC in the MOGISS total score within in each subject over the treatment period [ Time Frame: 5 weeks ]
    Defined as the daily total of all 8 individual symptom scores within each subject
  • Frequency, severity, and duration of overall GI events using the MOGISS. [ Time Frame: 5 weeks ]
    Frequency, severity and duration of overall GI events will be completed using the MOGISS for each week of study treatment as well as for the overall study treatment period.
  • Safety and tolerability outcomes: incidence rates of all non GI-adverse events [ Time Frame: 5 weeks ]
    Subject incidence rates of all non GI-adverse events
Original Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
  • The number of days that a subject experiences at least one GI symptom (as reported on the MOGISS) with a severity score of at least 1. [ Time Frame: 5 weeks ]
  • Safety and tolerability outcomes: incidence rates of all non GI-adverse events [ Time Frame: 5 weeks ]
    Subject incidence rates of all non GI-adverse events
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Compare GI Tolerability Following Oral Administration of Bafiertam™ or Tecfidera to Healthy Volunteers
Official Title  ICMJE A Randomized, Double-Blind Study to Compare Gastrointestinal Tolerability Following Oral Administration of Bafiertam™ (Monomethyl Fumarate) or Tecfidera® (Dimethyl Fumarate) to Healthy Male and Female Volunteers
Brief Summary

The primary objective of the study is to compare in healthy subjects, the GI tolerability of bioequivalent doses of Bafiertam™(monomethyl fumarate) and its pro-drug Tecfidera® (dimethyl fumarate).

Secondary objective of this study is to compare the safety and tolerability of Bafiertam™ and Tecfidera® when administered orally following bioequivalent dose regimens in healthy subjects.

Detailed Description Subjects randomized (1:1) to either Bafiertam (monomethyl fumarate) or Tecfidera (dimethyl fumarate) will enter a double-blind titration period where they will receive either Bafiertam 95 mg twice daily (BID) or Tecfidera 120 mg BID for 7 days. Following the titration period, they will enter a maintenance period in which they will receive Bafiertam 190 mg BID or Tecfidera 240 mg BID for 4 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Drug: Bafiertam
    Over-encapsulated capsule to mask treatment
    Other Name: monomethyl fumarate
  • Drug: Tecfidera
    Over-encapsulated capsule to mask treatment
    Other Name: dimethyl fumarate
Study Arms  ICMJE
  • Experimental: Bafiertam
    oral capsules administered twice daily
    Intervention: Drug: Bafiertam
  • Active Comparator: Tecfidera
    oral capsules administered twice daily
    Intervention: Drug: Tecfidera
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 13, 2020)
210
Original Estimated Enrollment  ICMJE
 (submitted: July 16, 2019)
200
Actual Study Completion Date  ICMJE October 19, 2019
Actual Primary Completion Date October 19, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males or non-pregnant females.
  2. Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator.
  3. Body Mass Index within 18.0 - 34.0 kg/m2, inclusive

Exclusion Criteria:

  1. Known history or presence of any clinically significant hepatic, renal/genitourinary, Gastrointestinal (GI), cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator.
  2. Clinically significant history or presence of any clinically significant GI pathology unresolved GI symptoms, or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within 7 days prior to first study drug administration, as determined by the PI/Sub-Investigator.
  3. Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
  4. Subject with abnormal baseline laboratory values deemed to be clinically significant by the Investigator.
  5. Lymphocyte count <1.5x 10^9/L.
  6. Known history or presence of: Alcohol abuse or dependence within one year prior to first study drug administration; Drug abuse or dependence; Hypersensitivity or idiosyncratic reaction to DMF, its excipients, and/or related substances; Progressive multifocal leukoencephalopathy (PML); Fanconi syndrome; Flushing (e.g., warmth, redness, itching, and burning sensation); Low white blood cell count (lymphopenia);
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04022473
Other Study ID Numbers  ICMJE BLS-11-109
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Time Frame: Beginning 6 months and ending 12 months following article publication.
Access Criteria:

Researchers who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

The stated purpose of the analysis as to be for individual participant data meta-analysis.

Responsible Party Banner Life Sciences LLC
Study Sponsor  ICMJE Banner Life Sciences LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kathleen Doisy, MD BioPharma Services, Inc
PRS Account Banner Life Sciences LLC
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP